We have demonstrated that human diploid fibroblasts (HDF) use both glucose and glutamine as primary energy sources for growth. Furthermore, 15% of the metabolized glutamine is accumulated as lactate. The enzymes of the malate-aspartate shuttle as well as phosphoenolpyruvate carboxykinase, pyruvate carboxylase, malic enzyme are involved in this route of glutamine catabolism. Further research will establish how these enzymes are regulated in fibroblasts by growth cycle and glucose concentrations. Additional studies will delineate the classes of substances capable of supporting growth of cultured cells and their competition with glucose and glutamine metabolism. The effect of growth factors on glutamine utilization will be studied in fibroblasts from controls, patients with lacticacidosis and infants dying from the Sudden Infant Death Syndrome. The latter have been proposed to be deficient in the enzyme phosphoenolpyruvate carboxykinase.